• A practical guide to cancer subclonal reconstruction from DNA sequencing

      Tarabichi, M.; Salcedo, A.; Deshwar, A. G.; Ni Leathlobhair, M.; Wintersinger, J.; Wedge, David C; Van Loo, P.; Morris, Q. D.; Boutros, P. C.; The Francis Crick Institute, London, UK. (2021)
      Subclonal reconstruction from bulk tumor DNA sequencing has become a pillar of cancer evolution studies, providing insight into the clonality and relative ordering of mutations and mutational processes. We provide an outline of the complex computational approaches used for subclonal reconstruction from single and multiple tumor samples. We identify the underlying assumptions and uncertainties in each step and suggest best practices for analysis and quality assessment. This guide provides a pragmatic resource for the growing user community of subclonal reconstruction methods.
    • Nanomedicine: photo-activated nanostructured titanium dioxide, as a promising anticancer agent

      Lagopati, N.; Evangelou, K.; Falaras, P.; Tsilibary, E. C.; Vasileiou, P. V. S.; Havaki, S.; Angelopoulou, A.; Pavlatou, E. A.; Gorgoulis, Vassilis G; Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Faculty of Medicine, School of Health Science, National and Kapodistrian University of Athens, 75, Mikras Asias Str., Goudi, GR 11527 Athens, Greece; (2020)
      The multivariate condition of cancer disease has been approached in various ways, by the scientific community. Recent studies focus on individualized treatments, minimizing the undesirable consequences of the conventional methods, but the development of an alternative effective therapeutic scheme remains to be held. Nanomedicine could provide a solution, filling this gap, exploiting the unique properties of innovative nanostructured materials. Nanostructured titanium dioxide (TiO2) has a variety of applications of daily routine and of advanced technology. Due to its biocompatibility, it has also a great number of biomedical applications. It is now clear that photo-excited TiO2 nanoparticles, induce generation of pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) that have been proven to damage cancer cells, triggering controlled cellular processes. The aim of this review is to provide insights into the field of nanomedicine and particularly into the wide context of TiO2-NP-mediated anticancer effect, shedding light on the achievements of nanotechnology and proposing this nanostructured material as a promising anticancer photosensitizer.
    • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

      Conti, D. V.; Darst, B. F.; Moss, L. C.; Saunders, E. J.; Sheng, X.; Chou, A.; Schumacher, F. R.; Olama, A. A. A.; Benlloch, S.; Dadaev, T.; et al. (2021)
      Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
    • Cellular senescence and failure of myelin repair in multiple sclerosis

      Koutsoudaki, P. N.; Papadopoulos, D.; Passias, P. G.; Koutsoudaki, P.; Gorgoulis, Vassilis G; Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens (2020)
      Remyelination is a physiological response to demyelinating events aiming to restore saltatory conduction and preserve axonal integrity. Resident oligodendrocyte precursor cells (OPC) of the CNS tissue under appropriate conditions are mobilized to proliferate, migrate, and differentiate, in order to produce new myelin sheaths in the demyelinated lesion. In multiple sclerosis (MS), the most common immune-mediated demyelinating disease, remyelination efficiency declines with increasing age and disease duration. As myelin regeneration attempts in clinical trials so far are scarce, and have been met with limited success, the need to explore new remyelinating strategies is more compelling. Recently, ageing and cellular senescence have been implicated in the pathophysiology of a number of neurodegenerative diseases, including multiple sclerosis. Evidence on OPC senescence brings forward the possibility of exploiting cellular senescence as a possible target for promoting the endogenous remyelinating capacity of the CNS. Here we discuss the data indicating how cellular senescence affects remyelination, and the putative benefits to be drawn through the use of senolytic or senomorphic therapies targeting senescent cell populations in MS.
    • CRISPR-Cas9-mediated gene silencing in cultured human epithelia

      Gago, S.; Overton, Nicola L D; Bowyer, P.; Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Core Technology Facility, The University of Manchester, Manchester, UK. (2021)
      CRISPR/Cas9 technology enables rapid and efficient genome editing in a variety of experimental systems. Genome editing using CRISPR/Cas9 has become an increasingly popular genetic engineering tool due to (1) an extensive array of commercial ready-to-use CRIPSR/Cas9 systems, (2) improved efficiency of cell delivery, and (3) the possibility to do multigene editing. Here, we describe a method to introduce single gene disruption in lung bronchial epithelial cells. This approach can be used to study host factors important for pathogen interaction or to identify and study genetic markers determining susceptibility to fungal disease.
    • Reference bias in the Illumina Isaac aligner

      Cornish, A. J.; Chubb, D.; Frangou, A.; Hoang, P. H.; Kaiser, M.; Wedge, David C; Houlston, R. S.; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SM2 5NG (2020)
    • Early detection of melanoma in specialised primary care practice in Australia

      Green, Adèle C; Pandeya, N.; Morton, S.; Simonidis, J.; Whiteman, D. C.; Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006, Australia; CRUK Manchester and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, (2020)
      Background: Primary care skin cancer clinics facilitate early treatment of melanoma in Australia. We investigated the clinical and histopathological features of melanomas diagnosed and treated in an established clinic in Brisbane. Methods: Retrospective audit of medical records of patients diagnosed with in situ or invasive primary cutaneous melanoma in a primary care clinic specializing in skin cancer, 2000-2017. Demographic and clinical data were standardly extracted by a medically-trained investigator. We used descriptive analyses to assess characteristics of patients and melanomas, and examine surgical management according to tumour thickness. Results: Of 380 patients (median age 57 years; 57 % male) newly diagnosed with 497 histologically-confirmed primary cutaneous melanomas, 369 were in situ and 128 invasive. Of the 369 in situ melanomas, 143 (39 %) were on the trunk and 87 (24 %) on the head and neck; 247 (67 %) were diagnosed by shave biopsy; and 141 (38 %) referred for wide local excision (WLE). Of the 128 invasive melanomas, only 21 (16 %) had thickness ≥ 0.8 mm and these occurred more often on head and neck than thin invasive melanomas (p = 0.02). The majority of invasive melanomas were diagnosed by excision biopsy, and WLE was carried out in a median of 3 days (melanomas ≥ 0.8 mm) and 2 days (<0.8 mm). The doctor detected the majority of in situ (83 %) and thin invasive (73 %) melanomas during surveillance, compared with 48 % of thicker invasive melanomas ≥ 0.8 mm (p < 0.001). Conclusion: In Australia, specialised primary care practice plays a major role in detection and treatment of early primary melanoma.
    • A RAC-GEF network critical for early intestinal tumourigenesis

      Pickering, K. A.; Gilroy, K.; Cassidy, J. W.; Fey, S. K.; Najumudeen, A. K.; Zeiger, L. B.; Vincent, D. F.; Gay, D. M.; Johansson, J.; Fordham, R. P.; et al. (2021)
      RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.
    • The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens

      Canton, J.; Blees, H.; Henry, C. M.; Buck, M. D.; Schulz, O.; Rogers, N. C.; Childs, E.; Zelenay, Santiago; Rhys, H.; Domart, M. C.; et al. (2020)
      Type 1 conventional dendritic (cDC1) cells are necessary for cross-presentation of many viral and tumor antigens to CD8+ T cells. cDC1 cells can be identified in mice and humans by high expression of DNGR-1 (also known as CLEC9A), a receptor that binds dead-cell debris and facilitates XP of corpse-associated antigens. Here, we show that DNGR-1 is a dedicated XP receptor that signals upon ligand engagement to promote phagosomal rupture. This allows escape of phagosomal contents into the cytosol, where they access the endogenous major histocompatibility complex class I antigen processing pathway. The activity of DNGR-1 maps to its signaling domain, which activates SYK and NADPH oxidase to cause phagosomal damage even when spliced into a heterologous receptor and expressed in heterologous cells. Our data reveal the existence of innate immune receptors that couple ligand binding to endocytic vesicle damage to permit MHC class I antigen presentation of exogenous antigens and to regulate adaptive immunity.
    • Use of immunomodulating drugs and risk of cutaneous melanoma: a nationwide nested case-control study

      Berge, L. A. M.; Andreassen, B. K.; Stenehjem, J. S.; Heir, T.; Karlstad, Ø.; Juzeniene, A.; Ghiasvand, R.; Larsen, I. K.; Green, Adèle C; Veierød, M. B.; et al. (2020)
      Purpose: Cutaneous melanoma is among the fastest growing malignancies in Norway and ultraviolet radiation (UVR) exposure is the primary environmental risk factor. Immunomodulating drugs can increase skin photosensitivity and suppress immune responses, and by such mechanisms influence melanoma risk. We, therefore, aimed to examine the associations between use of immunomodulating drugs and melanoma risk, at a nationwide population level. Patients and methods: In the Cancer Registry of Norway, we identified all cases aged 18-85 with a first primary cutaneous melanoma diagnosed in 2007-2015 (n=12,106). These were matched to population controls from the Norwegian National Registry 1:10 (n=118,564), on sex and year of birth using risk set sampling. Information on prescribed drugs (2004-2015) was obtained by linkage to the Norwegian Prescription Database (NorPD). Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between use of immunomodulating drugs (immunosuppressants and corticosteroids) and melanoma risk, adjusted for ambient UVR and other drug use. Results: Compared with ≤1 prescription, use of ≥8 prescriptions of immunosuppressants was associated with increased risk of melanoma (RR 1.50, 95% CI 1.27, 1.77). Similar associations were found for subgroups of immunosuppressants: drugs typically prescribed to organ transplant recipients (OTRs) (RR 2.02, 95% CI 1.35, 3.03) and methotrexate (RR 1.27, 95% CI 1.04, 1.55). Similar results were found for high levels of cumulative doses and across all histological subtypes. Use of corticosteroids was not associated with melanoma risk. Conclusion: We found a positive association between use of immunosuppressants and melanoma risk, with the highest risk seen for drugs prescribed to OTRs. Knowledge about this risk increase is important for physicians and users of these drugs, for intensified surveillance, awareness and cautious sun exposure.
    • Survival in patients with multiple primary melanomas: Systematic review and meta-analysis

      Peek, G.; Olsen, C. M.; Baade, P.; Youlden, D. R.; Aitken, J. F.; Green, Adèle C; Khosrotehrani, K.; Queensland Skin and Cancer Foundation, Queensland Institute of Dermatology, South-Brisbane, Queensland, Australia. (2020)
      Background: The literature surrounding survival of patients with multiple primary melanomas (MPM) yields variable and opposing findings, constrained by statistical challenges. Objectives: To critically examine the available literature regarding survival of patients with MPM compared with a single primary melanoma and detail statistical methods used. Methods: Electronic searches were performed of PubMed, Embase, Web of Science, and Scopus, with cross-checking of references, for the period January 1956 to June 2019. Studies published in English examining survival in patients with multiple melanomas were included. Case studies and small case series were excluded. Results: There were 14 studies eligible for inclusion. Conclusions on survival varied markedly depending on the statistical method used. Four studies that accounted for survival bias by partitioning the survival time were included in the quantitative review, with 3 of these reporting a survival disadvantage for MPM, whereas the fourth showed no difference in survival. The pooled hazard ratio was 1.39 (95% confidence interval, 1.07-1.81) but with significant heterogeneity (I2 = 96.8%, Phet < .001). Limitations: Studies showed significant heterogeneity in methodology. Conclusion: When data were analyzed with robust statistical methods, patients with MPM had a survival disadvantage compared with patients with a single primary melanoma.
    • Sample pooling strategies for SARS-CoV-2 detection

      Lagopati, N.; Tsioli, P.; Mourkioti, I.; Polyzou, A.; Papaspyropoulos, A.; Zafiropoulos, A.; Evangelou, K.; Sourvinos, G.; Gorgoulis, Vassilis G; Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National Kapodistrian University of Athens (NKUA), Greece. (2020)
      The worldwide COVID-19 pandemic outburst has caused a serious public health issue with increasing needs of accurate and rapid diagnostic and screening testing. This situation requires an optimized management of the chemical reagents, the consumables, and the human resources, in order to respond accurately and effectively, controlling the spread of the disease. Testing on pooled samples maximizes the number of tested samples, by minimizing the time and the lab supplies needed. The general conceptualization of the pooling method is based on mixing samples together in a batch. Individual testing is needed only if a specific pool exhibits a positive result. The development of alternative hybrid methods, based on "in house" protocols, utilizing commercially available consumables, in combination with a reliable pooling method would provide a solution, focusing on the better exploitation of the personnel and the lab supplies, allowing for rapid screening of a population in a reasonably short time.
    • Impact of lineage plasticity to and from a neuroendocrine phenotype on progression and response in prostate and lung cancers

      Rubin, M. A.; Bristow, Robert G; Thienger, P. D.; Dive, Caroline; Imielinski, M.; Department for BioMedical Research, University of Bern and Inselspital, 3010 Bern, Switzerland; Bern Center for Precision Medicine, University of Bern and Inselspital, 3010 Bern, Switzerland. (2020)
      Intratumoral heterogeneity can occur via phenotype transitions, often after chronic exposure to targeted anticancer agents. This process, termed lineage plasticity, is associated with acquired independence to an initial oncogenic driver, resulting in treatment failure. In non-small cell lung cancer (NSCLC) and prostate cancers, lineage plasticity manifests when the adenocarcinoma phenotype transforms into neuroendocrine (NE) disease. The exact molecular mechanisms involved in this NE transdifferentiation remain elusive. In small cell lung cancer (SCLC), plasticity from NE to nonNE phenotypes is driven by NOTCH signaling. Herein we review current understanding of NE lineage plasticity dynamics, exemplified by prostate cancer, NSCLC, and SCLC.
    • Making connections: p53 and the cathepsin proteases as co-regulators of cancer and apoptosis

      Soond, S. M.; Savvateeva, L. V.; Makarov, V. A.; Gorokhovets, N. V.; Townsend, Paul A; Zamyatnin, A. A., Jr.; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya Str. 8-2, 119991 Moscow, Russia. (2020)
      While viewed as the "guardian of the genome", the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. As an important step in determining the fate of cells in response to cytotoxicity or during stress response, lysosomal-mediated cell death has also become strongly interwoven with the key components that give the lysosome functionality in the form of the cathepsin proteases. While a number of articles have been published highlighting the independent input of p53 or cathepsins to cellular homeostasis and disease progression, one key area that warrants further focus is the regulatory relationship that p53 and its isoforms share with such proteases in regulating lysosomal-mediated cell death. Herein, we review recent developments that have shaped this relationship and highlight key areas that need further exploration to aid novel therapeutic design and intervention strategies.
    • Integrative p53, micro-RNA and cathepsin protease co-regulatory expression networks in cancer

      Soond, S. M.; Kozhevnikova, M. V.; Townsend, Paul A; Zamyatnin, A. A., Jr.; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya str. 8-2, 119991 Moscow, Russia. (2020)
      As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. While this area is still in its infancy in relation to general cathepsin gene regulation, we review the current p53-regulated micro-RNAs that are generating significant interest through their regulation of cathepsin proteases, thereby strengthening the link between activated p53 forms and cathepsin gene regulation. Additionally, we extend our understanding of this developing relationship to how such micro-RNAs are being utilized as diagnostic or prognostic tools and highlight their future uses in conjunction with cathepsin gene expression as potential biomarkers within a clinical setting.
    • Development impact analysis of gemtuzumab ozogamicin for the treatment of CD33-positive acute myeloid leukemia

      Reynolds, K. A.; Schlessinger, D. I.; Yanes, A. F.; Godinez-Puig, V.; Chen, B. R.; Kurta, A. O.; Cotseones, J. K.; Chiren, S. G.; Iyengar, S.; Ibrahim, S. A.; et al. (2020)
      Background: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. Objective: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. Methods: One hundred nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, respectively, in two rounds of Delphi exercises. Outcomes scored 'critically important' (scored 7,8, or 9) by 70% of patients and 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. Results: A core set of seven outcomes was finalized at the consensus meeting: serious or persistent adverse events, patient-reported quality of life, complete response, partial response, recurrence-free survival, progression-free survival, and disease-specific survival. Conclusions: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes
    • NADPH oxidases are required for full platelet activation in vitro and thrombosis in vivo but dispensable for plasma coagulation and hemostasisand apoptosis

      Vara, D.; Mailer, R. K.; Tarafdar, Anuradha; Wolska, N.; Heestermans, M.; Konrath, S.; Spaeth, M.; Renné, T.; Schröder, K.; Pula, G.; et al. (2020)
      Objective: Using 3KO (triple NOX [NADPH oxidase] knockout) mice (ie, NOX1-/-/NOX2-/-/NOX4-/-), we aimed to clarify the role of this family of enzymes in the regulation of platelets in vitro and hemostasis in vivo. Approach and Results: 3KO mice displayed significantly reduced platelet superoxide radical generation, which was associated with impaired platelet aggregation, adhesion, and thrombus formation in response to the key agonists collagen and thrombin. A comparison with single-gene knockouts suggested that the phenotype of 3KO platelets is the combination of the effects of the genetic deletion of NOX1 and NOX2, while NOX4 does not show any significant function in platelet regulation. 3KO platelets displayed significantly higher levels of cGMP-a negative platelet regulator that activates PKG (protein kinase G). The inhibition of PKG substantially but only partially rescued the defective phenotype of 3KO platelets, which are responsive to both collagen and thrombin in the presence of the PKG inhibitors KT5823 or Rp-8-pCPT-cGMPs, but not in the presence of the NOS (NO synthase) inhibitor L-NG-monomethyl arginine. In vivo, triple NOX deficiency protected against ferric chloride-driven carotid artery thrombosis and experimental pulmonary embolism, while hemostasis tested in a tail-tip transection assay was not affected. Procoagulatory activity of platelets (ie, phosphatidylserine surface exposure) and the coagulation cascade in platelet-free plasma were normal. Conclusions: This study indicates that inhibiting NOXs has strong antithrombotic effects partially caused by increased intracellular cGMP but spares hemostasis. NOXs are, therefore, pharmacotherapeutic targets to develop new antithrombotic drugs without bleeding side effects.
    • First-in-human phase i study of MP0250, a first-in-class DARPin drug candidate targeting VEGF and HGF, in patients with advanced solid tumors

      Baird, R. D.; Linossi, C.; Middleton, M.; Lord, S.; Harris, A.; Rodón, J.; Zitt, C.; Fiedler, U.; Dawson, K. M.; Leupin, N.; et al. (2020)
      Purpose: A first-in-human study was performed with MP0250, a DARPin drug candidate. MP0250 specifically inhibits both vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) with the aim of disrupting the tumor microenvironment. Patients and methods: A multicenter, open-label, repeated-dose, phase I study was conducted to assess the safety, tolerability, and pharmacokinetics of MP0250 in 45 patients with advanced solid tumors. In the dose-escalation part, 24 patients received MP0250 as a 3-hour infusion once every 2 weeks at five different dose levels (0.5-12 mg/kg). Once the maximum tolerated dose (MTD) was established, 21 patients were treated with a 1-hour infusion (n = 13, 8 mg/kg, once every 2 weeks and n = 8, 12 mg/kg, once every 3 weeks) of MP0250 in the dose confirmation cohorts. Results: In the dose-escalation cohort, patients treated with 12 mg/kg MP0250 once every 2 weeks experienced dose-limiting toxicities. Therefore, MTD was 8 mg/kg once every 2 weeks or 12 mg/kg once every 3 weeks. The most common adverse events (AEs) were hypertension (69%), proteinuria (51%), and diarrhea and nausea (both 36%); hypoalbuminemia was reported in 24% of patients. Most AEs were consistent with inhibition of the VEGF and HGF pathways. Exposure was dose-proportional and sustained throughout the dosing period for all patients (up to 15 months). The half-life was about 2 weeks. Signs of single-agent antitumor activity were observed: 1 unconfirmed partial response with a time to progression of 23 weeks and 24 patients with stable disease, with the longest duration of 72 weeks and a median duration of 18 weeks. Conclusion: MP0250 is a first-in-class DARPin drug candidate with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other anticancer therapies.
    • Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project

      Millen, G. C.; Arnold, R.; Cazier, J. B.; Curley, H.; Feltbower, R. G.; Gamble, A.; Glaser, A. W.; Grundy, R. G.; Lee, L. Y. W.; McCabe, Martin G; et al. (2020)
      Background: Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK. Methods: Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital. Results: Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%. Conclusions: Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.
    • COVID-19 and myeloma clinical research - experience from the CARDAMON clinical trial

      Camilleri, M.; Sive, J.; Wilson, W.; Pang, G.; Jenner, R.; Phillips, Elizabeth H; Popat, R.; Ramasamy, K.; Bygrave, C.; Dadaga, T.; et al. (2020)